The Baltimore Longitudinal Study of Aging (BLSA) was established in 1958 and is one the oldest prospective studies of aging in the USA and the world. The mission of the BLSA is to learn what happens to people as they get old and how to sort out changes due to aging from those due to disease or other causes. The Early Markers of Alzheimer's Disease program continues to perform cognitive assessments and establish research diagnoses of Alzheimer's Disease for BLSA participants. This information is used in multiple collaborative research projects conducted by intramural and extramural investigators, including our studies of brain aging and neuroimaging biomarkers of cognitive decline and AD. Over the last year, we have continued cognitive assessments of BLSA participants, as well as diagnostic case conferences to establish research diagnoses of cognitive impairment. We have continued to investigate possible modifiers of cognitive aging, risk for dementia, and the presence of Alzheimer's pathology at autopsy. We collaborate with both intramural and extramural investigators, such as Dr. Michelle Mielke at the Mayo Clinic. With Dr. Mielke, we have published two papers to date describing factors that modify longitudinal changes in sphingolipids, including both ceramides and sphingomeylins, in BLSA participants. We are investigating changes in sphingolipids over time in relation to cognitive decline and the risk for Alzheimer's disease. In addition, we have continued to collaborate with the CHARGE consortium to identify specific genetic markers that contribute to individual differences in memory and executive function. We also have expanded our collaborative efforts with Dr. Stephanie Studenski and Luigi Ferrucci and their teams to investigate the associations between age changes in cognitive and motor function. In a recent paper, postdoctoral fellow Dr. Teresa Tian showed that variation in gait speed, measured by lap time variation, was cross-sectionally associated with executive function in 811 older adults aged 60 and older. Independent of age, sex, and mean lap time or overall walking speed, higher gait variability was associated with slower psychomotor speed, and among those with faster walking speed, gait variation was associated with worse performance on a complex measure of cognitive flexibility. In collaboration with Dr. Thambisetty and his team, we have shown in BLSA Early Markers participants that that midlife adiposity predicts earlier onset of Alzheimer's disease, higher levels of neurofibrillary tangles at autopsy, and trends toward higher levels of amyloid burden using in vivo PET amyloid imaging scans. These findings suggest that being overweight and obese at midlife may predict earlier accumulation of Alzheimer's neuropathology and symptom onset and that maintenance of a healthy weight could delay the onset of Alzheimer's disease.